The relationship between the expression of Pituitary Adenylate Cyclase-Activating Polypeptide & its receptors and apoptosis in human pituitary adenomas

垂体腺苷酸环化酶激活多肽（PACAP）最初是从下丘脑组织中分离出来的，基于其刺激培养的垂体前叶细胞产生cAMP的能力。最近的研究表明，PACAP在脑细胞凋亡中起功能作用。然而，PACAP在调节人垂体腺瘤细胞凋亡中的作用尚未被证实。对培养的人垂体腺瘤细胞系HP75和表达三种主要PACAP受体的人垂体腺瘤细胞进行分析，发现PACAP-38和PACAP-27均能抑制tgf - 51诱导的细胞凋亡。PACAP受体拮抗剂PACAP 6？38 （PACAP I型受体拮抗剂）和(p-chloro-D-Phe6, Leu17)-VIP （PACAP II型受体拮抗剂）阻断了PACAP-38对转化生长因子s1 （TGF-s1）诱导的细胞凋亡的抑制作用，证实了PACAP作用的特异性。细胞周期蛋白依赖性激酶抑制剂p16、p21、p27的免疫细胞化学分析显示，p27仅在人垂体腺瘤中表达。这些结果表明，PACAP是tgf - 51诱导的人垂体腺瘤细胞系HP75细胞凋亡的高度特异性抑制剂。垂体腺瘤通过实时RT-PCR表达p16、p21、p27和p53 mrna。而在蛋白水平上，只有p27在人垂体腺瘤中表达。此外，cyclin D3作为癌基因在人垂体腺瘤中高表达，而cyclin B1和D1不表达。

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from hypothalamic tissue based on its ability to stimulate cAMP production in cultured anterior pituitary cells. Recent studies have suggested a functional role for PACAP in the apoptosis of brain cells. However, the role of PACAP in regulating apoptosis in human pituitary adenomas has not previously been examined. Analysis of the cultured human pituitary adenoma cell line HP75 and human pituitary adenomas, which expresses all three major PACAP receptors, showed that both PACAP-38 and PACAP-27 inhibited TGF-s1-induced apoptosis. Treatment with the PACAP receptor antagonists PACAP 6?38 (PACAP type I receptor antagonist) and (p-chloro-D-Phe6, Leu17)-VIP (PACAP type II receptor antagonist) blocked the effects of PACAP-38 on the inhibition of transforming growth factor-s1 (TGF-s1)-induced apoptosis, confirming the specificity of the role of PACAP. Immunocytochemical analysis of the cell cycle cyclin-dependent kinase inhibitor p16, p21, p27 showed only p27 expression in human pituitary adenomas. These results indicate that PACAP is a highly specific inhibitor of TGF-s1-induced apoptosis in the HP75 human pituitary adenoma cell line. Pituitary adenomas expressed p16, p21, p27 and p53 mRNAs by real time RT-PCR. However, in protein level, only p27 expressed in human pituitary adenomas. Moreover, cyclin D3 as oncogene highly expressed in human pituitary adenomas but not cyclin B1 or D1.